Rishi Sunak’s communication chief quit on Friday.
“I would like to take this opportunity to thank the Prime Minister for his support and his leadership.”
She added: “The team he has built around him is dedicated and focused because those are the qualities he inspires. I also want to thank my colleagues - No10 is a demanding and high pressure place to work - yet the professionalism and talent they display every day is exceptional.”
Ms de Botton, who had a decade-long career as a senior broadcast political journalist, was hired by the Prime Minister as his director of communications a few days after he entered Downing Street.
Unlike an impartial civil servant, she was a special adviser able to give political advice to ministers, defend the Government's actions and criticise opposition parties.
She announced her resignation shortly after it was claimed on the Guido Fawkes political website that No10 Chief of Staff Liam Booth-Smith had allegedly suggested to special advisers they should quit if they did not believe the Tories could win the next election.
There was no suggestion that this was Ms de Botton’s view and the two matters are understood not to be linked.
She was deputy head of politics at Sky News for five years until 2017 and then worked at ITV News as head of politics and then as head of news.
Her resignation comes a day after Mr Sunak announced minor changes to his ministerial team following the resignation of Defence Secretary Ben Wallace, who is stepping down from frontline politics.
The appointment of Grant Shapps, one of the Prime Minister's closest cabinet allies, as Defence Secretary was seen a slight reset ahead of the next general election.
A wider reshuffle is expected in the next coming months.
Ms de Botton was seen to have played a key role in helping to stabilise the Government under Mr Sunak after Liz Truss’ disastrous, brief administration.
But the Tories are still trailing Labour by about 20 points in the polls.
Attempts to close the gap, including with weeks this summer focusing on key issues for voters, such as the “small boats” crossing the Channel, appeared to have made little headway.
Ms de Botton’s departure threatened to overshadow some more positive news for the Government on the economy on Friday.
Official figures showed the UK economy had already returned to its pre-Covid levels by the end of 2021.
The Office for National Statistics said it was revising its estimate for gross domestic product (GDP) that year after getting access to new data.
By the last three months of 2021, the economy is now estimated to have been 0.6 per cent larger than 2019 levels, compared to a previous estimate that it was 1.2 per cent smaller.
The revision means the UK's economy is now believed to have grown by 8.5 per cent during 2021, compared to the previous estimate of 7.6 per cent, the ONS said.
Chancellor Jeremy Hunt tweeted: “Some important news today: the ONS have published new stats which show that Britain’s economic performance coming out of COVID was much stronger than originally thought.”
Mr Sunak messaged in response: “I‘m proud of the support I put in place as Chancellor during Covid. From the furlough scheme to the Culture Recovery Fund, we protected millions of jobs and got the economy growing again.
“Now, we need to halve inflation and stick to our plan.”
But the cost-of-living crisis is still hitting millions of households, with mortgage payments and rents having soared for many of them.
The Government also appears at times to be dogged by crises and controversies, with the latest one over potentially unsafe concrete used in some school buildings and hospitals, as well as strikes ongoing by doctors, rail staff and other public sector workers.